Fragment-Based Drug Design and Drug Repositioning Using Multiple Ligand Simultaneous Docking (MLSD): Identifying Celecoxib and Template Compounds as Novel Inhibitors of Signal Transducer and Activator

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• 作者：Huameng Li ; Aiguo Liu ; Zhenjiang Zhao ; Yufang Xu ; Jiayuh Lin ; David Jou ; Chenglong Li
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：August 11, 2011
• 年：2011
• 卷：54
• 期：15
• 页码：5592-5596
• 全文大小：828K
• 年卷期：v.54,no.15(August 11, 2011)
• ISSN：1520-4804

文摘

We describe a novel method of drug discovery using MLSD and drug repositioning, with cancer target STAT3 being used as a test case. Multiple drug scaffolds were simultaneously docked into hot spots of STAT3 by MLSD, followed by tethering to generate virtual template compounds. Similarity search of virtual hits on drug database identified celecoxib as a novel inhibitor of STAT3. Furthermore, we designed two novel lead inhibitors based on one of the lead templates and celecoxib.